This invention relates to nuclear magnetic resonance (NMR) imaging, and more particularly, to methods and compositions for enhancing NMR imaging.
The recently developed technique of NMR imaging encompasses the detection of certain atomic nuclei utilizing magnetic fields and radio-frequency radiation. It is similar in some respects to x-ray computed tomography (CT) in providing a cross-sectional display of the body organ anatomy with excellent resolution of soft tissue detail. As currently used, the images produced constitute a map of the distribution density of protons and/or their relaxation times in organs and tissues. The technique of NMR imaging is advantageously non-invasive as it avoids the use of ionizing radiation.
While the phenomenon of NMR was discovered in 1945, it is only relatively recently that it has found application as a means of mapping the internal structure of the body as a result of the original suggestion of Lauterbur (Nature, 242, 190-191, 1973). The fundamental lack of any known hazard associated with the level of the magnetic and radio-frequency fields that are employed renders it possible to make repeated scans on vulnerable individuals. Additionally, any scan plane can readily be selected including transverse, coronal and sagittal sections.
In an NMR experiment, the nuclei under study in a sample (e.g. protons) are irradiated with the appropriate radio-frequency (RF) energy in a highly uniform magnetic field. These nuclei as they relax subsequently emit RF at a sharp resonant frequency. The coupling frequency (RF) of the nuclei depends on the applied magnetic field.
According to known principles, nuclei with appropriate spin when placed in an applied magnetic field (B, expressed generally in units of gauss or tesla (10.sup.4 gauss)) align in the direction of the field. In the case of protons, these nuclei precess at a frequency f=42.6 B MHz at a field strength of 1 Tesla. At this frequency, an RF pulse of radiation will excite the nuclei and can be considered to tip the net magnetization out of the field direction, the extent of this rotation being determined by the pulse duration and energy. After the RF pulse, the nuclei "relax" or return to equilibrium with the magnetic field, emitting radiation at the resonant frequency. The decay of the signal is characterized by two relaxation times, i.e., T.sub.1, the spin-lattice relaxation time or longitudinal relaxation time, that is, time taken by the nuclei to return to equilibrium along the direction of the externally applied magnetic field, and T.sub.2, the spin-spin relaxation time associated with the dephasing of the initially coherent precession of individual proton spins. These relaxation times have been established for various fluids, organs and tissues in different species of mammals.
In NMR imaging, scanning planes and slice thickness can be selected. This permits high quality transverse, coronal and sagittal images to be obtained directly. The absence of any moving parts in NMR imaging equipment promotes a high reliability. It is believed that NMR imaging has a greater potential than CT for the selective examination of tissue characteristics in view of the fact that in CT, x-ray attenuation coefficients alone determine image contrast whereas at least four separate variables (T.sub.1, T.sub.2, proton density and flow) may contribute to the NMR signal. For example, it has been shown (Damadian, Science, 171, 1151, 1971) that the values of the T.sub.1 and T.sub.2 relaxation in tissues are generally longer by about a factor of 2 in excised specimens of neoplastic tissue compared with the host tissue.
By reason of its sensitivity to subtle physiochemical differences between organs and/or tissues, it is believed that NMR may be capable of differentiating different tissue types and in detecting diseases which induce physiochemical changes that may not be detected by x-ray or CT which are only sensitive to differences in the electron density of tissue. NMR images also enable the physician to detect structures smaller than those detectable by CT and thereby provide comparable or better spatial resolution.
As noted above, two of the principal imaging parameters are the relaxation times, T.sub.1 and T.sub.2. For protons (or other appropriate nuclei), these relaxation times are influenced by the proton's environment (e.g., viscosity, temperature).
These two relaxation phenomena are essentially mechanisms whereby the initially imparted radiofrequency energy is dissipated to the surrounding environment. The rate of this energy loss or relaxation can be influenced by certain other nuclei which are paramagnetic and chemical compounds incorporating these paramagnetic nuclei may substantially alter the T.sub.1 and T.sub.2 values for nearby protons. The extent of the paramagnetic effect of a given chemical compound is a function of the environment within which it finds itself.
As the use of NMR imaging grows in acceptance, there will be a corresponding increase in the need for enhancing NMR images and for favorably influencing T.sub.1 and T.sub.2 relaxation times through the use of agents which enhance NMR images.